Significant advances were made in discovering mechanisms of retrovirus-induced immunosuppression in the Friend virus model. We found that CD8 cells mediated protection from immunosuppression via a gamma interferon-dependent mechanism. Conversely IL-10 was found to be involved in susceptibility to virus-induced suppression of antibody responses. We were able to restore the ability of infected mice to mount antibody responses to secondary infections by blockade of the IL-10 receptor. In addition, interferon gamma was found to be dispensable for recovery from the acute phase of Friend virus-induced disease, but necessary for control of persistent virus. Interferon gamma-deficient mice were unable to keep virus loads at low steady state levels and eventually developed erythroleukemia. Interestingly, the interferon gamma-deficient mice actually mounted quicker antibody responses than the wild type mice and controlled acute virus loads with faster kinetics. However, by 6 to 8 weeks post infection spleen virus loads in the interferon gamma-deficient mice rose above wild type levels and continued to rise over the next 8 weeks until all mice had levels of infectious centers 10 to 100 times those in the wild type mice.